Alpha-synuclein pathology in the “weaver” mouse, a genetic model of dopaminergic denervation

TL;DR

This study shows that the 'weaver' mouse model of Parkinson's disease exhibits alpha-synuclein pathology, including increased phosphorylation, during established dopaminergic degeneration.

Contribution

The study confirms the 'weaver' mouse as a genetic model for studying alpha-synuclein pathology in Parkinson's disease progression.

Findings

Increased Serine 129 phosphorylation of alpha-synuclein is observed in midbrain, striatum, and cortex.

Alpha-synuclein pathology is present at postnatal day 100 in the 'weaver' mouse model.

The 'weaver' mouse is validated as a model for studying Parkinson's disease pathogenesis.

Abstract

Alpha-synuclein plays a pivotal role in Parkinson’s disease (PD) pathogenesis, with α-synuclein aggregates/oligomers being identified as toxic species and phosphorylation at Serine 129 promoting aggregation/oligomerization. We investigated the biochemical profile of α-synuclein in the “weaver” mouse, a genetic PD model. Our results revealed increased Serine 129 phosphorylation in the midbrain, striatum, and cortex at a phase of established dopaminergic degeneration on postnatal day 100. These results indicate α-synuclein pathology already at this stage and the potential for age-related progress. Our findings confirm that the “weaver” mouse is an invaluable genetic model to study α-synuclein pathogenesis during PD progression.

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